The long range goal of this work is to obtain a better understanding of the factors in human cell mediated immunity which are important in organ allotransplantation. Emphasis will be placed on improving, evaluating and using a new cytotoxicity method to measure the effector are of allograft immunity in vitro. This method takes advantage of the fact that lymphocytes sensitized by allogeneic cells are specifically cytotoxic to lymphocytes isogeneic to the sensitizing cells and presumably to cells processing the same histocompatibility antigens or crossreacting antigens as those of the sensitizing cells. Experiments will be conducted to determine if a meaningful correlation exists between cytotoxicity, the mixed leukocyte culture reaction, HL-A typing, and graft rejection. During this time we will attempt to improve the cytotoxicity assay by increasing the sensitivity and developing a micro-method. By utilizing the cytotoxicity phase of the system, sensitization having take place in vivo, a suitable assay is provided for studying cellular and humoral (blocking) factors in the post-operative transplant patient against the transplanted organ. Using the mother-foetus relationship as a model allograft tolerance in humans, studies will be conducted with the cytotoxicity system described in this proposal to determine the state of cell mediated immunity in the mother, foetus and newborn and the role of blocking factors in this system.